HER2-directed therapy following ctDNA-identified ERBB2 amplification in patients with advanced gastroesophageal cancer: exploration of real-world outcomes

Background

Data on patient outcomes with human epidermal growth factor receptor 2 (HER2)-directed therapy after detection of ERBB2 amplification (ERBB2 amp) by circulating tumor DNA (ctDNA) are lacking in advanced gastroesophageal adenocarcinoma (aGEA). We report real-world outcomes in aGEA patients who received HER2-directed therapy following ctDNA-identified ERBB2 amp.

Materials and methods

Real-world evidence was sourced from the GuardantINFORM (Guardant Health) database which includes aggregated health claims and de-identified results from patients undergoing ctDNA testing [Guardant360 (G360)]. Patients with aGEA, ERBB2 amp, and one or more claims for treatment after index G360 were included; those with prior HER2-directed therapy were excluded. Real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS) were assessed in months. The Cox regression model adjusted for age, gender, and lines of treatment since diagnosis assessed differences in outcomes.

Results

We identified 215 patients with ERBB2 amp, out of which 135 (63%) received HER2-directed therapy following ctDNA-identified ERBB2 amp. rwTTD and rwTTNT were significantly improved in patients receiving HER2-directed therapy compared with those who did not [rwTTD: 5.8 versus 1.9 months, hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.34-0.65, P < 0.01; rwTTNT: 9.4 versus 6.3 months, HR 0.55, 95% CI 0.37-0.81, P < 0.01]. No differences in rwOS were observed (rwOS: not reached versus 22 months, HR 0.67, 95% CI 0.41-1.08, P = 0.10).

Conclusions

Detection of ERBB2 amp by ctDNA testing is feasible and may confer improved outcomes in patients receiving HER2-directed therapy, presenting an opportunity to increase HER2-directed therapy utilization in patients with aGEA.